Evaluation of matrix microsampling methods for therapeutic drug candidate quantification in discovery-stage rodent pharmacokinetic studies

• Published in: Bioanalysis Vol. 6; no. 16; pp. 2135 - 2146
• Main Authors: Soto, Marcus, Pham, Roger, Almon, Valerie, Wagner, Mylo, Primack, Ronya, Ponce, Manuel, Meyer, James, James, Christopher A, Salyers, Kevin L, Retter, Marc W
• Format: Journal Article
• Language: English
• Published: England 01.08.2014
• Subjects: Animals; Benzothiazoles - blood; Benzothiazoles - pharmacokinetics; Blood Specimen Collection - methods; Chromatography, High Pressure Liquid - methods; Drug Discovery; Male; Mice; Pharmacokinetics; Pyrimidines - blood; Pyrimidines - pharmacokinetics; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry - methods; Triazoles - blood; Triazoles - pharmacokinetics
• ISSN: 1757-6180; 1757-6199
• DOI: 10.4155/bio.14.184

AMG 517 or 1-aminobenzotriazole were quantified by LC-MS/MS from low blood/plasma volumes for rat pharmacokinetic (PK) characterization in order to qualify manual/automated dried blood spot (DBS) sampling and plasma separation capillary sampling. In addition, mouse serial automated blood sampling was compared with standard composite sampling. AMG 517 or 1-aminobenzotriazole was administered to rats or mice and multiple microsampling techniques were used to obtain blood or plasma. PK parameters derived from DBS and whole blood-obtained drug concentrations were within 7% for manual DBS and 20% for automated DBS. Plasma PK parameters derived from capillary or standard plasma-obtained drug concentrations differed by 6%. Plasma PK parameters obtained from serial automated blood sampling or manual composite sampling were within 20%. Collectively, these results suggest that the microsampling applications that were investigated are attractive approaches for quantifying drug candidates in low matrix volumes that can be successfully employed within discovery-stage rodent PK studies.